Introduction Introduction - primary cutaneous amyloidosis Demographics Causes Clinical features Complications Diagnosis Differential diagnoses Treatment Outcome
Amyloidosis is the term used for a group of diseases where various insoluble proteins (amyloid) accumulate in one or more body organs causing dysfunction of the organ system. Organs often affected include the heart, kidney, gastrointestinal tract, nervous system, and skin.
Amyloidosis of the skin is called cutaneous amyloidosis. In this condition, amyloid or amyloid-like proteins are deposited in the dermis.
There are three important types of amyloidosis.
Primary cutaneous amyloidosis (PCA), also termed primary localized cutaneous amyloidosis, encompasses a group of skin conditions characterised by extracellular deposition of heterogenic amyloid protein in previously normal skin, without internal organ involvement. It is distinct and unrelated to systemic amyloidosis. Based on morphology and histology, PCA is subclassified into:
There are also several rare atypical variants, such as:
The precise cause of PCA remains unclear, especially at the molecular level of amyloid fibril formation. However, lichen and macular amyloidosis are described as being of keratinocyte origin that results from apoptosis of keratinocytes with locally produced amyloid protein.
Scratching, scrubbing, and sun exposure are thought to be contributory factors. Familial tendency occurs in 10–15% of cases, and the involvement of oncostatin-M-receptor (OSMR) and IL-31 receptor A mutation has been reported.
In nodular amyloidosis, amyloid light chain (AL) deposits are produced from local plasma cell proliferation.
The clinical features of primary cutaneous amyloidosis will depend on the subtype.
Lichen amyloidosis
Nodular amyloidosis
Both lichen and macular amyloidosis have a benign behaviour and do not spread to other parts of the body or internal organs.
The diagnosis of PCA subtypes can be made on the characteristic clinical appearance with itch at typical sites (e.g. itchy papules over shin leg for LA, and itchy hyperpigmented macules over upper back for MA).
Skin biopsy may identify amyloid deposits in the skin on H & E stained sections, Congo-red stain under polarised light illumination (apple-green birefringence), and immunohistochemistry.
Typical histologic findings show:
Lichen amyloidosis especially in early or mild stage may be difficult to differentiate from other pruritic papular skin disorders, such as:
Macular amyloidosis is to be differentiated from other hyperpigmentary disorders, such as:
Nodular amyloidosis can mimic various cutaneous and subcutaneous nodules, including:
Due to the lack of controlled trials, there are no accepted treatment strategies. With all therapies, there is recalcitrance and recurrences. Treatment focuses on relief of aesthetic disfigurement and pruritus.
Useful for extensive lesions when topical treatments are impractical or unresponsive — (used off-label):
Primary cutaneous amyloidosis is often resistant to therapy, and if it does improve, it is likely to recur when any therapy is discontinued.
